This application seeks support for an R21 Translational Research Network designed to integrate human developmental neuroscience with basic developmental and child clinical research to generate heuristic models and testable hypotheses about preschool psychopathology and its neural substrates. Early childhood provides a particularly useful starting point for the delineation of relevant phenotypes and a nosology informed by neuroscience and developmental theory. This is because neural, psychological and behavioral processes converge during this developmental period to create the potential for self-regulation. Recent methodologic advances in neuroscience and developmentally-informed clinical research now make it possible to characterize clinical problems in young children and their underlying pathophysiology. However, substantial intellectual and methodologic effort is required to combine these heretofore disparate lines of research. To this end, the specific aims of the Network are to (I) Create an intellectual environment in which neuroscientists join with development and clinical scientists to develop integrated conceptual models of the phenotypes and endophenotypes of anxiety and disruptive behavior in young children. In particular, Network discourse will focus on (a) distinguishing normative variations in temperament from clinical levels of anxious and disruptive behavior and, (b) delineating the role of perturbations in the emotion-attention interface as a key substrate of these emerging clinical problems and, (II) Conduct collaborative studies to provide an empirical foundation for a translational research agenda for the study of preschool psychopathology. Pilot activities will include (a) exploring Network questions within existing preschool samples of the Network and, (b) developing and piloting an integrated assessment battery that assesses key processes at multiple levels, from neural to contextual, with a small sample (N=60) of clinically-referred, temperamentally- and clinically at- risk and typically-developing preschool children. The intellectual and empirical activities of the Network are designed to serve as the foundation for a multi-site Translational Research Center in Behavioral Sciences that examines preschool psychopathology and its substrates. [unreadable] [unreadable] [unreadable]